Unmet needs in squamous cell carcinoma of the lung: potential role for immunotherapy

Abstract

Squamous cell carcinoma of the lung accounts for 20-30% of non-small cell lung cancers (NSCLC). Despite the differences in disease characteristics between squamous and non-squamous NSCLC, both have historically been treated similarly in the clinic. Recently approved drugs have revealed differences in activity and safety profiles across histologic subtypes and have applicability in treating non-squamous, but not typically squamous, NSCLC. Exploration of immune checkpoints--co-inhibitory molecules used to regulate immune responses--has resulted in novel immunotherapies designed to interrupt signaling through the cytotoxic T lymphocyte-associated antigen-4 or programmed cell death protein-1 pathways on lymphocytes. Modulation of these pathways can lead to restored antitumor immune responses, and preliminary evidence shows that agents targeting these pathways have activity in lung cancer, including squamous NSCLC.

Fig. 1

Clinical efficacy of phased ipilimumab + carboplatin/paclitaxel by histologic subtype in patients with NSCLC [49]. irPFS, progression-free survival (PFS) by modified WHO (mWHO) criteria and overall survival (OS) in the phase II randomized study of ipilimumab administered either in a phased schedule or currently with paclitaxel/carboplatin in patients with NSCLC, analyzed by histologic subtype. Comparison of the phased ipilimumab arm versus placebo arm. Phased ipilimumab plus paclitaxel/carboplatin appeared to have a greater effect on patients with squamous histology than those with non-squamous histology. The hazard ratio (HR) point estimates for irPFS, mWHO-PFS, and OS were significantly smaller with phased ipilimumab plus paclitaxel/carboplatin in the squamous population compared with the non-squamous population; however, small sample size warrants caution in interpretation. Reproduced with permission from Zielinski et al. [49]